Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• hydrophobic cavity and chiral sites during a catalytic process [24][25]. Recently, we have reported a series of different functionalized organic catalysts based on calixarenes [26][34][35][36][37][38]. For example, we have been developed a calix[4]arene-based L-proline catalyst able to catalyze aldol

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• ones to the cationic charged residues, the purple circles to the polar uncharged residues and the green circle to a proline residue. The black line denotes hydrophilic and hydrophobic faces of the amphipathic structures. Red arrows show the mutation positions. MTT assays using Dec-NH2 and its synthetic

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• . reported the synthesis of a series of prolinamide and hydroxyprolinamide organocatalysts based on the calix[4]arene scaffold (Figure 8) [59]. Treatment of Boc-protected-L-proline or hydroxyproline with various aminocalix[4]arenes under one of the appropriate coupling conditions and subsequent deprotection

• good yields (up to >99%) with up to 97% ee and up to 85:15 dr (Scheme 20). In order to exploit the hydrophobic cavity of the calixarene platform in aldol reactions, two novel p-tert-butylcalix[4]arene-based chiral organocatalysts bearing L-proline units on the lower rim have been reported by Yilmaz et

• al. [60]. Coupling of calixarene diamine 60 with Boc-L-proline 74 or calixarene diacid chloride 76 with N-(2-aminoethyl)-N'-(tert-butoxycarbonyl)-L-prolinamide 77 and subsequent deprotection afforded catalysts 75 and 78 in good yields (Scheme 21). In 2014, an upper rim functionalized calix[4]arene

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• intramolecular cross-coupling of C−H bonds in 95 using catalytic chiral iodine 12 for the synthesis of a diverse array of spirooxindoles 96. Ishihara’s catalyst was modified by using an (S)-proline derivative to achieve a high level of enantioselectivity in the presence of peracetic acid (Scheme 21) [70]. They

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• depicted in Figure 2, PQS (4a) has an OH moiety that allows for its linkage to the organocatalyst proline 4b. Also, PQS has a lipophilic component that acts as a reaction solvent for hydrophobic dienes. The latter feature allows aldol reactions to take place efficiently in water. The aldol reaction between

• cyclohexanone and p-nitrobenzaldehyde was chosen to verify the performance of this nanoreactor. PQS-proline and the analogous mixed diester derivative of 4-hydroxyproline were prepared and tested in this process. The aldol product was achievable only by using the proline compound 4b, therefore different

• the diffusion through the membrane was not possible. Moreover, the crosslinking enabled stabilization of the enzymes, which remained active also after 10 days. Polymersome nanoreactors have also been used to perform many types of non-enzymatic catalytic reactions, such as the proline-catalyzed

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• stereocontrol in alcoholytic catalytic asymmetric desymmetrizations of meso-cyclic anhydrides is of special interest [1][2][3][4][5][6][7]. Major families originating from natural products include cinchona alkaloids [8][9][10][11][12][13][14][15][16][17] and proteinogenic α-amino acids such as proline [18][19

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• TFA as promoter at 80 °C to 140 °C. A three-component reaction of 5-aminopyrazole 16, 4-hydroxycoumarin (50) and aldehydes 47 was studied by Liu et al. [55] in various solvents like acetonitrile, dichloromethane, toluene and DMSO in the presence of catalysts like ZrCl4, InCl3, FeCl3, L-proline etc

• catalysts like L-proline, InCl3 and ZrCl4 also resulted in the formation of o-hydroxyphenylpyrazolo[3,4-b]pyridine derivatives 85 but no product was formed in iodine- and acetic acid-catalyzed reactions (Scheme 22). Huang et al. [70] investigated a three-component reaction of β-ketonitriles 15, 5

• -1-(methylthio)-2-nitroethenamine (96) was studied by Gunasekaran et al. [77] (Scheme 28) in ethanol in presence of 30 mol % L-proline as catalyst at 78 °C which resulted in the production of pyrazolo[3,4-b]pyridine derivatives 97 in excellent yields. Jiang et al. [78] have investigated a microwave

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• in good yield starting from the N-benzylation of L-proline in the presence of KOH, then activation of the carboxylic acid functionality of 10 using SOCl2 at low temperature, followed by condensation with 2-aminobenzophenone (Scheme 2). Complexation of 11 with nickel nitrate and glycine under basic

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• Polarimetry was used to investigate the binding abilities of a chiral calix[4]resorcinarene derivative, bearing L-proline subunits, towards a set of suitably selected organic guests. The simultaneous formation of 1:1 and 2:1 host–guest inclusion complexes was observed in several cases, depending on both the

• can be generally achieved by linking suitable donor groups to the aromatic scaffold. Among the virtually countless examples available in recent literature, L-proline-modified CAs constitute an interesting subject of study [19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Proline-based systems

• in general have been proven excellent stereoselective organocatalysts [33][34][35][36][37][38][39][40]. In particular, CA derivatives bearing proline units (on both the upper and the lower rim) have been tested as catalysts for asymmetric aldol reactions in water [28][29][30][33]. Similar derivatives

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• fluorescence push–pull system would be destroyed. To confirm this, we modified 1 to provide a peptidic substrate for an enzyme. The serine protease DPP-4 was used as the test enzyme because its substrate specificity is clear: it hydrolyses the C-terminal of proline or alanine second to the N-terminal of the

• -protected glycine was condensed with proline methyl ester under microwave irradiation. Subsequent hydrolysis of the ester gave N-protected Gly-Pro-OH (6). Condensation of dipeptide 6 with 1 was achieved using the corresponding acid chloride. Deprotection of the amino group was achieved by treatment with

• ]-L-proline methyl ester (5): N-Phtaloylglycine (4 mmol), 1-hydroxybenzotriazole (4.4 mmol) and N-ethyl-N’(3-dimethylaminopropyl)carbodiimide hydrochloride (10 mmol) were placed in a microwave vial. To the microwave vial was added anhydrous DMF (8 mL) and anhydrous N,N-diisopropylethylamine (20 mmol

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• favour a linear and less hindered shape [14]. A notable exception is found in the case of the proline, where the s-cis isomer is favoured [15]. With the monofluoroalkene moiety, it is possible to mimic selectively one or the other isomer as no equilibrium exists between them. As such, the (Z

• give the (Z)-monofluoroalkene 67 as a single isomer (dr > 95:5). Conversion of the ester into the corresponding Weinreb amide, followed by addition of an organolithium reagent gave the corresponding ketone 69. Four further steps gave the ring skeleton for the proline residue of 71, i.e., formation of

• , which is a promising inhibitor of the non-structural protein NS5A, an interesting target of the chronic hepatitis C virus [52]. The monofluoroalkene replaced the amide group, and the use of a dipeptide isostere containing a proline residue favoured a γ-turn substructure which is necessary for the

Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts

• Jan Wallbaum and
• Daniel B. Werz

Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254

• ][3][4][5][6][7]. Initially, proline and proline-derived catalysts have been widely used in asymmetric iminium and enamine organocatalysis [8][9][10][11][12]. Since the beginning of the 21th century imidazolidinone-based organocatalysts developed by MacMillan and co-workers, which are easily

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• profiles can be altered by the presence of even a single fluorinated amino acid in the sequence. Perhaps the most studied molecules exhibiting such effects are the proline analogues, with the proline-to-fluoroproline exchange providing the first proof-of-principle and experimental basis for a number of

• very low yield of the desired product 5 (4%). The monofluoro- and trifluoroethyl esters 3 and 5 were then prepared via the corresponding chloranhydride, which was generated as described (Scheme 1B) [51]. The drawback of this method is that generation of chloranhydride from N-acetylated proline leads to

• states, s-trans and s-cis (Scheme 2), with the former being thermodynamically preferred in most cases [66][67]. The intrinsic contextual preference in the amide isomerism around the proline residue is usually characterized using small molecular models such as esters of N-acetylproline, similar to those

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• reactions with E-1b is hydrazine and its derivatives. The parent hydrazine used as the hydrate reacts with E-1 in ethanol at room temperature, and in the case of diisopropyl dicyanofumarate (E-1c), the crystalline enehydrazine was isolated in 82% yield [62]. In addition, the N-benzyl-protected (S)-proline

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• , France Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France 10.3762/bjoc.13.217 Abstract Ball milling was exploited to prepare a substituted proline building block by mechanochemical nucleophilic substitution

• . Subsequently, the mechanocoupling of hindered proline amino acid derivatives was developed to provide proline–proline dipeptides under solvent-free conditions. A deprotection–cyclization sequence yielded the corresponding diketopiperazines that were obtained with a high stereoselectivity which could be

• feature, used for the preparation of biologically active peptides and peptidomimetics [7], for applications in organocatalysis [8][9][10], and for the preparation of novel materials [11][12]. An interesting sub-family of these compounds are DKPs derived from the amino acid proline and its analogues, which

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• -free conditions were performed using a combination of (S)-binam-L-Pro (A, 5 mol %) and benzoic acid (10 mol %) as organocatalyst [49]. Juaristi and co-workers investigated the mechanistic aspects of α,α-dipeptide derivatives of a (S)-proline- (A′)-catalyzed asymmetric aldol reaction (Scheme 2b) under

• -(S)-proline derived catalyst [49]. b) Report using α,α-dipeptide-based catalyst [50]. Mechanochemical Michael reaction [51]. Mechanochemical organocatalytic asymmetric Michael reaction [52]. Mechanochemical Morita–Baylis–Hillman (MBH) reaction [53]. Mechanochemical Wittig reactions [55

A concise and practical stereoselective synthesis of ipragliflozin L-proline

• Shuai Ma,
• Zhenren Liu,
• Jing Pan,
• Shunli Zhang and
• Weicheng Zhou

Beilstein J. Org. Chem. 2017, 13, 1064–1070, doi:10.3762/bjoc.13.105

• 10.3762/bjoc.13.105 Abstract A concise and practical stereoselective synthesis of ipragliflozin L-proline was presented starting from 2-[(5-iodo-2-fluorophenyl)methyl]-1-benzothiophene and 2,3,4,6-tetra-O-pivaloyl-α-D-glucopyranosyl bromide without catalyst via iodine–lithium–zinc exchange. The overall

• yield was 52% in three steps and the product purity was excellent. Two key diastereomers were prepared with efficient and direct access to the α-C-arylglucoside. Keywords: arylzinc derivative; β-C-arylglucoside; diastereomer impurity; ipragliflozin L-proline; stereoselective synthesis; Introduction

• , (ipragliflozin L-proline 1, (1S)-1,5-anhydro-1-C-{3-[(1-benzothiophen-2-yl)methyl]-4-fluorophenyl}-D-glucitol (2S)-pyrrolidine-2-carboxylic acid (1:1), Figure 1), was launched into the Japanese market in January 2014 [7][8]. Due to its efficacy and safety, 1 can be used as monotherapy or in combination with

Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and ³J_HH coupling constant analyses

• Weslley G. D. P. Silva,
• Carolyne B. Braga and
• Roberto Rittner

Beilstein J. Org. Chem. 2017, 13, 925–937, doi:10.3762/bjoc.13.94

• derivatives of tryptophan [20], phenylalanine and tyrosine [21], aspartic acid [22], proline [23] and histidine [24]. These studies have provided significant results to understand the importance of the corresponding amino acids in processes in which they take part in the polypeptide chain. Furthermore, these

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• L-proline at room temperature for three days proceeded sluggishly, leading to the desired product in a very low yield. Gratifyingly, when the L-proline-catalyzed aldol reaction was performed at 70 °C for one day, the TLC indicated the complete consumption of aldehyde 3, and the generated 4,5-anti

• excellent anti-selectivity for the L-proline-catalyzed aldol reaction can be explained by the Houk–List transition state model [43][44][45]. Compound 13 was then acetylated to afford differentially protected ketoheptose building block 2 in 83% yield. The structure of 2 was unambiguously confirmed by 1H, 13C

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• , entries 9 and 10). Reactions performed with other catalysts (L-proline and pyrrolidine) gave lower yields of 3a than those using 1 mol % of Et2NH (Table 1, entry 7 vs entries 11 and 12). From Table 1, optimum reaction conditions to obtain 1-(5-methyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazol-4-yl)ethan

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• selected as a benchmark reaction to study their behaviour as organocatalysts. Compounds with a related structure prepared from proline by Diez et al. have proven to work well as organocatalysts in the Michael addition of cyclohexanones to nitrostyrenes [19][20]. We first tested organocatalysts OC1–OC4 in

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• combination of CuI and bidentate ligand could promote the conversion of aryl halides to the corresponding phenols in a mixed solvent system of DMSO/H2O (1:1). Using iodobenzene as model substrate, various ligands were successfully tested: L-proline (yield 70%), 2-hydroxyacetophenone (yield 85%), N,N-dimethyl

• , the Qi group reported a similar protocol to achieve the coupling of aryl iodides and thiourea by CuI/L-proline-catalyzed reaction in the presence of Cs2CO3 as base in DMSO [98]. In 2004, the Itoh group demonstrated that Pd2(dba)3/Xantphos (L14) could catalyze the coupling of aryl halides and aryl or

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• ability, chromophoric properties, and antitumor activity as well [40]. We compared several CuI-based catalytic systems in the arylation of amine 3b with 4-iodotoluene as a model substrate. We found out that the CuI/L-proline combination with K2CO3 led to the target aniline 4 in excellent yield (Scheme 3

• anthraquinones. Further attempts to apply the Cu-based catalytic system in this reaction with L-proline and other commonly used N,N, N,O, and O,O bidentate ligands were fruitless. Previously, some of us successfully used the classic conditions of the Buchwald–Hartwig amination for the preparation of bis-amino

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• tricyclic skeleton that bears a newly formed pyrrolidine, similar to proline. The post-translational dimethylallylation of two tryptophan residues of a cyclic peptide, kawaguchipeptin A, from cyanobacteria has also been reported. Interestingly, the modified tryptophan residues of kawaguchipeptin A have the

• either a geranyl or farnesyl group at the gamma position to form tricyclic skeleton that bears a newly formed pyrrolidine, which is similar to proline (Figure 3A) [26][27][28]. The posttranslational modification of ComX pheromones with an isoprenoid plays an essential role for specific quorum sensing